Nuclear factor-kappa B pathway and response in a phase II trial of bortezomib and docetaxel in patients with recurrent and/or metastatic head and neck squamous cell carcinoma

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Abstract
Background: Our previous study has shown that nuclear factor-kappa B (NF-κB)-signaling pathway was associated with a higher rate of recurrence in head and neck squamous cell carcinoma (HNSCC). The combination of bortezomib, an NF-κB inhibitor by inhibition of proteasomes, plus docetaxel was assessed for efficacy and toxicity. Materials and methods: Patients with recurrent and/or metastatic HNSCC were enrolled on a phase II bortezomib/docetaxel trial (bortezomib 1.6 mg/m2 and docetaxel 40 mg/m2 on days 1 and 8 of a 21-day cycle). Response was assessed using RECIST. Tissue specimens were evaluated for the presence of human papillomavirus (HPV) and expression of NF-κB-associated genes. Results: Twenty-one of 25 enrolled patients were assessable for response; one partial response (PR, 5%), 10 stable disease (SD, 48%) and 10 progressive disease (PD, 48%). Patients with PR/SD had significantly longer survival compared with patients with PD and the regimen was well tolerated. Only one of 20 tumors was positive for HPV. Patients with PD had higher expression of NF-κB and epidermal growth factor receptor-associated genes in their tumors by gene expression analysis. Conclusion: Further understanding of treatment resistance and interactions between bortezomib and docetaxel may provide novel approaches in managing HNSCC.
Funding Information
  • Robert J. and Helen C. Kleberg Foundation
  • National Institutes of Health (R01-DE-017982)
  • Millennium Pharmaceuticals, Inc

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